Chiral ligand-exchangers

Chiral ligand-exchange chromatography (CLEC) ° separates enantiomers by the formation of diastereomeric metal complexes. In a first instance the technique was mainly used for the separation of amino acids. Impressive results of the first separations gave rise to intensive investigation in the field and numerous publications appeared in the literature, which have been reviewed. 

TABLE 4 Examples of Chiral Separations in Chiral Ligand-Exchange Chromatography... 

Based on preliminary results from Helfferich130, further developments by Davankov and co-workers5 131 133 turned the principle of chelation into a powerful chiral chromatographic method by the introduction of chiral-complex-forming synlhetie resins. The technique is based on the reversible chelate complex formation of the chiral selector and the selectand (analyte) molecules with transient metal cations. The technical term is chiral ligand exchange chromatography (CLEC) reliable and complete LC separation of enantiomers of free a-amino acids and other classes of chiral compounds was made as early as 1968 131. 

Figure 19. Resolution of analytes by chiral ligand exchange chromatography (CLEC). A hydroxy acids (reprinted with permission from ref 138) B dansyl amino acids (reprinted with permission from ref 139),...

O Naobumi, H Kitahara, R Kira. Direct separation of enantiomers by high-performance liquid chromatography on a new chiral ligand-exchange phase. J Chromatogr 592 291-296, 1992. 

With the development of the chiral ligand exchange chromatography by Davan-kov, this technique has been used frequently for the chiral resolution of racemic compounds containing electron-donating atoms. It is useful for providing the basic information on the chiral resolution and, hence, is still in use. In spite of this, there are some limitations with this chiral resolution technique. The most... 

Type IB sorbents are chiral ligand exchangers. Several columns are commercially available with either proline, hydroxyproline, or valine and Cu(II) bonded to silica [256]. The binding is via a 3-glycidoxpropyl spacer Cu(II) needs to be added to the mobile phase to minimize the loss of copper from the sorbent. Silica modified by L-( + )-tartaric acid has also been synthesized. These columns generally have poor efficiency and analytes are limited to bidentate solutes [256]. 

Chiral ligand-exchange chromatography resolves enantiomers on the basis of their ability to complex with transition metal ions, such as copper, zinc, and cadmium, as illustrated by the separation of amino acid racemates using copper102 (Fig. 2.21). The principle of exchange is similar to that... 

Schmid et al. [60] demonstrated the enantiomer separation of underivatized amino acids on a monolithic chiral ligand-exchange phase by rod-CEC. The chiral stationary phase was prepared in situ in the capillary by polymerization of methacrylic acid, piperazine diacrylamide, vinylsulfonic acid and /V-(2-hydroxy-3-alloxypropyl)-L-4-hydroxyproline. The monolithic separation bed was covalently linked to the internal capillary wall and thus no frits were required. Fig. 9.13 shows the enantiomer separation of phenylalanine by (A) pure CEC (30 kV), (B) nano-LC (12 bar) and (C) pressure supported CEC (30 kV, 12 bar at the inlet vial). The shortest elution time was clearly obtained by pressure supported CEC, while the highest resolution was found in the pure CEC mode (CEC Rs = 2.11 nano-LC Rs = 0.98 pressure supported CEC Rs= 1.60). 

Beginning with this one example of a simple incursion into the realm of analytical applications of chiral ligand exchange in homogeneous media coupled with CD detection and the high level of selectivity observed, the prospects for even further enhancement appear to be very bright. Although... 

Type TV The diastereomeric complexes take place through metal complexes also known as chiral ligand exchange mechanism. 

Another molecular rect nition force is the metal-complex formation realized in chiral ligand-exchange chromatography (CLEC). The technique was first proposed by Helf-ferich ]400] and was turned into a powerful chromatographic technique by Davankov and co-workers [8,401 j. This technique is based on a reversible chelate-complex forma-... 

For a quite long period of time, chiral ligand-exchange chromatography (CLEC) has been the standard method for the enantioseparation of free amino acids. Meanwhile, other methods became available for these target molecules, such as teicoplanin or chiral crown-ether-based CSPs. However, for the enantioseparation of aliphatic a-hydroxy carboxylic acids, it is still one of the most efficient methods. 

Type IV When the solute is part of a diastereomeric metal complex (chiral ligand-exchange chromatography)... 

Chiral ligand-exchange chromatography is based on the formation of diastereomeric ternary complexes that involve a transition metal ion (M), usually copper II a single enantiomer of a chiral molecule (L), usually an amino acid and the eitantiomers of the racemic solute R and S). The diastereomeric mixed chelate complexes formed in this system are represented by the formulas L-M-R and L-M-S. When these complexes have different stabilities, the less stable complex is eluted first, and the enantiomeric solutes are separated. 

The most important technique for enantiomeric separation in TLC is chiral ligand-exchange chromatography (LEC). LEC is based on the copper(II) complex formation of a chiral selector and the respective optical antipodes. Differences in the retention of the enantiomers are caused by dissimilar stabilities of their diastereomeric metal complexes. The requirement of sufficient stability of the ternary complex involves five-membered ring formation, and compounds such as a-amino and a-hydroxy-acids are the most suitable. 

Chiral separation of racemic drugs is required by the pharmaceutical industry because different optical forms of the drugs often play different roles in their pharmacological action, metabohsm, and toxicity. Chiral ligand exchange chromatography plays an important role in this respect. 

Mathur, R. Bohra, S. Mathur, V. Narang, C.K. Mathur, N.K. Chiral ligand exchange chromatography on poly-glactomannan (guaran). Chromatographia 1992, 33, 336-338. 

Natalini, B., Marinozzi, M., Bade, K., Sardella, R.,Thomsen, C., Pellicciari, R. Preparative resolution of 1-aminoindan-1,5-dicarboxylic acid (AIDA) by chiral ligand-exchange chromatography. Chirality, 2004,16, 314-317. 

Davankov, V. A. 30 years of chiral ligand exchange. Enantiomer, 2000, 5, 209-223. 

Chiral ligand exchange chromatography utilizes immobilized tremsition metal complexes that selectively bind one enantiomer of the analyte, which is usually an amino acid. 

Arnold, F.H. Striegler, S. Sundaresan, V. Molecular and Ionic Recognition with Imprinted Polymers. In Chiral Ligand Exchange Adsorbents for Amines and Underiva-tized Amino Acids Bait-and-Switch Molecular Imprinting, ACS Symposium Series Bartsch, R., Maeda, M., Eds. 1998 Vol. 703, 109-118. 

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